Figure 4.

NAFLD as a bistable system involving a phenotypic switch from a hepatocyte to a “hybrid” adipocyte-like phenotype of the hepatocytes. (A) Schematic showing the phenotypic transition that may happen in the context of NAFLD where the disease can be highly diverse in terms of the extent of loss of hepatocytic and/or gain of adipocytic characteristics. (B) Bifurcation plots showing the phenotypic transitions, i.e., switch in the levels of HNF4A (top panel) and PPARG (bottom panel) when the degradation rate of PPARG is used as a bifurcation parameter. Solid blue lines denote the stable states, dotted red lines denote the unstable states of the system. Arrows indicate transitions between the two states. (C) Stochastic simulations of the core gene regulatory network showing switching in HNF4A and PPARG levels (degradation rate of PPARG = 0.08 hr⁻¹). (Image credit for “hepatocyte”, “fatty liver”, “adipocytes” in A and B: Wikimedia Commons).